Search

Simple Summary: Relapse following allogeneic hematopoietic stem cell transplantation (alloHSCT) for acute myeloid leukemia (AML) is the main reason for treatment failure. Most relapses occur during the first six months. We have observed in recent years that some patients relapse late, beyond 2 years after allograft. We sought to evaluate the frequency and the risk factors associated with these late relapses. We observed that these late relapses affect a significant number of patients, that the absence of chronic GvHD is more often associated. In addition, the intensity of the conditioning regimen does not seem to play a role and it is possible to re-treat successfully these patients. We conclude that prolonged monitoring after alloHSCT for AML is recommended. Late relapse, beyond 2 years following alloHSCT for AML, is rare. Among the 376 patients allografted for AML in our center between 1990 and 2016, 142 (38%) relapsed. The majority (68%) of relapses occurred during the first year following transplantation. Beyond 2 years after alloHSCT, relapse was observed in 26 patients, representing 6.9% of the whole transplanted cohort and 18.3% of the relapsing patients. Cytogenetics at relapse was available in 21 patients and remained for 15 of them concordant to that at diagnosis. The majority (85.7%) of the patients were in CR prior to transplant. Thirteen patients had grade 1–2 acute GvHD, while 13 other patients had grade 3–4 acute GvHD. None of these patients subsequently developed chronic GvHD. In multivariate analyses, a predictive factor of the absence of relapse 2 years after transplantation was the development of extensive chronic GVHD. Salvage therapy achieved new CR in 77% of these patients. We conclude that late relapse can affect a significant minority of patients allografted for AML, and the intensity of the conditioning regimen does not seem to have an impact on these relapses. Moreover, we were able to show that those patients can receive effective salvage therapy. [ABSTRACT FROM AUTHOR]

Medication non‐adherence (NA) after allogeneic hematopoietic cell transplantation (allo‐HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self‐reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non‐adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo‐HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA. [ABSTRACT FROM AUTHOR]

• Toxoplasmosis is a rare but potentially severe complication after allogeneic hematopoietic cell transplantation (HCT). • In this consecutive study of 419 allogeneic HCT recipients in France, the incidence of toxoplasmosis was 4%. • Seven of the 17 observed cases occurred before day 30 (median, day 22) and were especially severe compared with later cases, with 5 deaths. • We strongly recommend starting PCR screening with the transplant and eventually from conditioning in R+ patients to catch early reactivation. Among 419 consecutive allogeneic hematopoietic cell transplant recipients, we observed 17 (4.0%) cases of toxoplasmosis at a median time of day 45 (range, 6 to 322) after transplant. Seven of these 17 cases occurred before day 30 after transplant. Because of the lack of PCR screening and trimethoprim-sulfamethoxazole prophylaxis before engraftment, the diagnosis of toxoplasmosis was late, and 5 of these 7 patients died. Analyzing these cases, early Toxoplasma blood PCR screening, starting from transplant, is crucial. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity. [ABSTRACT FROM AUTHOR]

Introduction: The use of autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease (AD) patients has increased progressively worldwide. We retrospectively analysed the long-term outcome of AHSCT for AD reported to the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Method: All French AD patients (≥ 18 years at transplant) with a first AHSCT between 1997 and 2013 were included. Primary data were derived from the European Society for Blood and Marrow Transplantation (EBMT) registry, and additional data were obtained through a specific questionnaire designed for the study. Primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS) and non-relapse mortality (NRM). Results: Ninety-four AD patients were included, of whom 71% suffered from rheumatologic diseases (n = 67, including 56 systemic sclerosis (SSc)), 16% from neurological disease (n = 15, including 14 multiple sclerosis (MS)) and 13% from various other AD (n = 12). After a median (interquartile range, IQR) follow-up of 83 months (38–130), OS at 5 and 10 years were 77% (95% CI 68.5–86.2) and 64% (95% CI 51.7–76.3), and for PFS 51% (95% CI 40.4–61.6) and 44% (95% CI 32.8–55.3), respectively. Overall, NRM was 8.7% (95% CI 4.0–15.5) at day 100, 9.8% (95% CI 4.8–16.9) at 5 years and 13.6% (95% CI 6.9–22.5) at 10 years. Conclusions: This first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple myeloma included in prospective clinical trials are highly selected and therefore are expected not to be representative of the entire patient population. Additionally recommendations based on literature data and randomized trials are not systematically implemented in all patients. We sought to determine how patients hospitalized with a diagnosis of multiple myeloma are currently treated in France. Methods and findings: We performed a nation-wide search using the Programme de Médicalisation des Systèmes d’Information (PMSI) database which includes anonymous data for all patients hospitalized in France. We identified newly diagnosed cases in 2012 and analyzed the number and duration of hospital stays, coexisting conditions and treatment modalities with data available until the end of 2015. A diagnosis of multiple myeloma was determined for the first time during a hospitalization in France in 2012 in 6,282 patients (3,234 males and 3,048 females). The median age at diagnosis was 74 years (72 in males and 76 in females). A majority (55.3%) of patients were diagnosed and treated in a single heath center, including 37% in a university hospital and 52% in a non-university public hospital. Comorbidities potentially impacting on myeloma treatment were present in 57.5% of patients at diagnosis, and 15% had an associated diagnosis of another neoplasia. Intensive therapies with stem cell transplants were performed in 1033 patients (16% of total), the majority of which were aged less than 65 (881 patients, 85.3%). Stem cell transplants were performed more frequently in males while the distance between the site of residence and the transplant center had no impact on likelihood of receiving a transplant. Only 60% of patients less than 65 years old who were treated for their disease underwent intensification with stem cell transplant within the 4-year follow-up period. Conclusions: A large majority of patients hospitalized with a diagnosis of multiple myeloma are elderly, in particular females, and not eligible for transplants. Among the patients aged less than 65 and receiving therapy for their disease, 40% do not undergo transplants. These data emphasize the need for alternative therapies. [ABSTRACT FROM AUTHOR]

Killer cell immunoglobulin-like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to display a high polymorphism, such as their HLA ligands. Moreover, many studies conducted in mouse and human models have shown that NK-KIR receptors play an important role in haematopoietic stem cell transplantation (HSCT). A beneficial impact of peculiar KIR ligand (HLA) mismatching has been reported suggesting a role to this combinatory HLA-KIR polymorphism. It is thus important to investigate KIR diversity in various human populations. To this end, we used polymerase chain reaction-sequence-specific primers to evaluate KIR gene in five selected populations (France, Guadeloupe, Senegal, Finland and Réunion). Genotypic and haplotypic frequencies were computed, as well as genetic distances and dendrogram ( phylip package). These data illustrate the genetic relationship of these five populations through the KIR polymorphism. Results revealed a wide diversity in KIR gene frequencies in Guadeloupe and Réunion, and a high specificity in Senegal. The obtained dendrogram indicated small genetic distances between France, Guadeloupe and Réunion as well as between France and Finland. Senegal showed a distant genetic relationship with the other countries and, interestingly, an inverted ratio of coding/non-coding (KIR2DS4/1D) alleles compared with Caucasians. These data expose the broad diversity in KIR genes worldwide and show that KIR genes are pertinent tools in human population genetics. If the role of KIR donor–recipient incompatibilities is confirmed, KIR diversity according to ethnicity should be taken into account during the selection of HSCT donors. [ABSTRACT FROM AUTHOR]

The Etablissement franc¸ais des Greffes (EfG) is a state agency dealing with Public Health issues related to organ, tissue and cell transplantation in France. The evaluation of organ retrieval and transplantation activities, one of its missions, is supported by a national information system (EfG-IS). The EfG-IS is moving towards a new n-tier architecture comprising a terminology server for end-stage diseases, organ failure, dialysis and transplantation (EfG-TS). Following a preliminary audit of the existing coding system and in order to facilitate data recording, to improve the quality of information, to assume compatibility with terminological existing standards and to allow semantic interoperability with other local, national or international registries, a specific work has been conducted on the thesauri to integrate within the EfG-TS. In this paper focusing on the server's content rather than the container, we report first the functional and cognitive requirements that resulted from the preliminary audit. We then describe the methodological approach used to build the terminological server on “sound ontological foundations”. We performed the semantic analysis of existing medical terms to set up disease description frame-like structures. These diseases description frames consist of a limited set of nosological discriminating slots such as etiology, semiology, pathology, evolution and associated diseases. Each relevant medical term is thus associated to a concept defined and inserted within a hierarchy according to disease description frame resulting from the semantic analysis. Last, because this terminological server is shared by various transplant and dialysis centers to record patient data at different time point, contextualization of terms appeared as one of the functional requirements. We will also point out various contexts for medical terms and how they have been taken into account. [Copyright &y& Elsevier]

The Establissement français des Greffes (EfG) is a state agency dealing with Public Health issues related to organ, tissue and cell transplantation in France. EfG maintains a national information system (EfG-IS) for the evaluation of organ transplantation activities. The EfG-IS is moving toward a new n-tier architecture comprising a terminological server. Because this terminological server is shared by various kind of transplant teams and dialysis centers to record patients data at different time point, contextualisation of terms appeared as a functional requirement. We report in this paper various contexts for medical terms and how they have been taken into account.

Organ transplantations and tissue/cells grafts are efficacious in many diseases. Nevertheless, beside the risk due to the technology which permits to carry out transplantations and grafts (surgery, tissue and cells collection, preservation, storage, cell expansion technics, immunosuppressive regimen,...), the microbiology risk must be controlled throughout the process leading to the transplantation or the graft. The structures, the organizations, the procedures, the information network and the controls assure the control of the risk. It is the main objective of human product vigilance. Future regulations will define the objectives of this sanitary vigilance more precisely.